Effect of Metreleptin Therapy in the Treatment of Severe Insulin Resistance

June 9, 2023 updated by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Phase II Trial of Effect of Metreleptin Therapy in Severe Insulin Resistance

Study Description:

Patients with mutations of the insulin receptor have diabetes that is challenging to control with conventional therapies, leading to early morbidity and mortality. We hypothesize that recombinant leptin (metreleptin) in these patients will improve glycemia control.

Objectives:

Primary Objective: To determine if 1 year of metreleptin will improve glycemia control in patients with genetic defects of the insulin receptor. Secondary Objectives: To determine mechanisms by which metreleptin improves glycemia.

Endpoints:

Primary Endpoint: Hemoglobin A1c.

Secondary Endpoints: fasting plasma glucose, fasting insulin/C-peptide, glucose/insulin/C-peptide area under the curve during oral glucose tolerance test.

Study Population:

20 male or female patients with mutations of the insulin receptor, age (Bullet)5 years, at the NIH Clinical Center.

Description of Sites/Facilities Enrolling Participants: Description of Study Intervention:

NIH Clinical Center

Open label study of metreleptin, 0.2 mg/kg/day (max dose 0.24 mg/kg/day).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Study Description:

Patients with mutations of the insulin receptor have diabetes that is challenging to control with conventional therapies, leading to early morbidity and mortality. We hypothesize that recombinant leptin (metreleptin) in these patients will improve glycemia control.

Objectives:

Primary Objective: To determine if 1 year of metreleptin will improve glycemia control in patients with genetic defects of the insulin receptor. Secondary Objectives: To determine mechanisms by which metreleptin improves glycemia.

Endpoints:

Primary Endpoint: Hemoglobin A1c.

Secondary Endpoints: fasting plasma glucose, fasting insulin/C-peptide, glucose/insulin/C-peptide area under the curve during oral glucose tolerance test.

Study Population:

20 male or female patients with mutations of the insulin receptor, age (Bullet)5 years, at the NIH Clinical Center.

Description of Sites/Facilities Enrolling Participants: Description of Study Intervention:

NIH Clinical Center

Open label study of metreleptin, 0.2 mg/kg/day (max dose 0.24 mg/kg/day).

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

  • INCLUSION CRITERIA:
  • Provision of signed and dated informed consent form
  • Male or female, aged > 5 years
  • Clinically significant, severe insulin resistance caused by a known or suspected defect in the insulin receptor

  • Presence of at least one of the following metabolic abnormalities:

    • Fasting insulin >30 micro U/ml, or

    • Presence of diabetes as defined by the 2006 American Diabetes Association (ADA) criteria:

      • Fasting plasma glucose >= 126 mg/dL
      • 2 hour plasma glucose >= 200 mg/dL following a 75 gram (1.75g/kg if less than 40kg) oral glucose load, or
      • Diabetic symptoms with a random plasma glucose >= 200 mg/dL

EXCLUSION CRITERIA:

  • Pregnant at time of enrollment, women in their reproductive years who do not use an effective method of birth control, and women currently nursing or lactating within 6 weeks of having completed nursing.
  • Known infectious liver disease
  • Known HIV infection
  • Current alcohol or substance abuse
  • Active tuberculosis
  • Use of anorexigenic drugs
  • Other conditions which in the opinion of the clinical investigators would impede completion of the study.
  • Subjects who have a known hypersensitivity to E. Coli derived proteins.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Leptin Treatment
300 mg of study drug administered via subcutaneous (SC) injections.
Drug: Metreleptin
Administered SC twice/day to achieve physiological concentrations that will be effective in improving the severe state of insulin resistance seen in patients with genetic defects on their insulin receptor mutation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in HbA1C
Time Frame: Change at month 12 from baseline
Change in HbA1C at month 12 from baseline.
Change at month 12 from baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Fasting Insulin Level
Time Frame: Change at month 12 from baseline
Change in fasting insulin level at month 12 from baseline
Change at month 12 from baseline
Change in Fasting Blood Glucose
Time Frame: Change at month 12 from baseline
Change in fasting blood glucose at month 12 from baseline.
Change at month 12 from baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

  • Principal Investigator: Rebecca J Brown, M.D., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 21, 2003

Primary Completion (Actual)

October 23, 2019

Study Completion (Estimated)

January 1, 2030

Study Registration Dates

First Submitted

June 18, 2004

First Submitted That Met QC Criteria

June 18, 2004

First Posted (Estimated)

June 21, 2004

Study Record Updates

Last Update Posted (Actual)

June 13, 2023

Last Update Submitted That Met QC Criteria

June 9, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 030257
  • 03-DK-0257

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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